Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels

• Published in: Molecular genetics and metabolism reports 2017-06, Vol.11 (C), p.46-53
• Main Authors: Donida, Bruna, Marchetti, Desirèe P., Jacques, Carlos Eduardo Diaz, Ribas, Graziela, Deon, Marion, Manini, Paula, da Rosa, Helen Tais, Moura, Dinara Jaqueline, Saffi, Jenifer, Giugliani, Roberto, Vargas, Carmen Regla
• Format: Article
• Language: English
• Subjects: Keratan sulfate; Morquio A syndrome; Mucopolysaccharidosis type IVA; N-acetyl-galactosamine-6-sulfatase; Oxidative stress; Research Paper
• ISSN: 2214-4269; 2214-4269
• DOI: 10.1016/j.ymgmr.2017.04.005

Morquio A disease (Mucopolysaccharidosis type IVA, MPS IVA) is one of the 11 mucopolysaccharidoses (MPSs), a heterogeneous group of inherited lysosomal storage disorders (LSDs) caused by deficiency in enzymes need to degrade glycosaminoglycans (GAGs). Morquio A is characterized by a decrease in N-acetylgalactosamine-6-sulfatase activity and subsequent accumulation of keratan sulfate and chondroitin 6-sulfate in cells and body fluids. As the pathophysiology of this LSD is not completely understood and considering the previous results of our group concerning oxidative stress in Morquio A patients receiving enzyme replacement therapy (ERT), the aim of this study was to investigate oxidative stress parameters in Morquio A patients at diagnosis. It was studied 15 untreated Morquio A patients, compared with healthy individuals. The affected individuals presented higher lipid peroxidation, assessed by urinary 15-F2t-isoprostane levels and no protein damage, determined by sulfhydryl groups in plasma and di-tyrosine levels in urine. Furthermore, Morquio A patients showed DNA oxidative damage in both pyrimidines and purines bases, being the DNA damage positively correlated with lipid peroxidation. In relation to antioxidant defenses, affected patients presented higher levels of reduced glutathione (GSH) and increased activity of glutathione peroxidase (GPx), while superoxide dismutase (SOD) and glutathione reductase (GR) activities were similar to controls. Our findings indicate that Morquio A patients present at diagnosis redox imbalance and oxidative damage to lipids and DNA, reinforcing the idea about the importance of antioxidant therapy as adjuvant to ERT, in this disorder.